Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastroenteritis is one of the risk factors for developing irritable bowel syndrome (IBS). However, the precise mechanism of postinfectious IBS is still unknown. We tested the hypothesis that a combination of previous inflammation and repetitive colorectal distention (CRD) makes the colon hypersensitive and that treatment with a corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist blocks this colonic hypersensitivity. Rats were pretreated with vehicle or 2,4,6-trinitrobenzene sulphonic acid (TNBS) 6 weeks before CRD. For the CRD experiment, the colorectum was distended once a day for six consecutive days. The CRH-R1 antagonist (CP-154,526, 20 mg kg(-1)) or vehicle was injected subcutaneously 30 min before CRD. Visceral perception was quantified as visceromotor response (VMR) using an electromyograph. For histological examination, the rats were killed on the last day of CRD experiment, and haematoxylin and eosin-staining of colon segments was performed. Although from the first to the third day of CRD, VMRs increased in both the vehicle-treated rats and TNBS-treated rats, they were significantly higher in TNBS-treated rats than those in vehicle-treated controls. On the fifth day of CRD, however, VMRs in the vehicle-treated rats were significantly greater than those in TNBS-treated rats. Pretreatment of rats with CP-154,526 significantly attenuated the increase in VMR induced by repetitive CRD with previous inflammation. Finally, we found that repetitive CRD and repetitive CRD after colitis induced visceral inflammation. These results indicate that a combination of previous inflammation and repetitive CRD induces visceral hypersensitivity and that a CRH-R1 antagonist attenuates this response in rats.
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PMID:Corticotropin-releasing hormone receptor 1 antagonist blocks colonic hypersensitivity induced by a combination of inflammation and repetitive colorectal distension. 1876 32

So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro-benzene-sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC-IBS) and compared it with the TNBS-induced and CUMS-induced models. TC-IBS showed a pronounced depression phenotype with increased corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC-IBS, accompanied by increased serum 5-hydroxytryptamine (5-HT) level and colonic 5-HT receptor 3A (5-HT3AR)/5-HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens-1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5-HT3AR antagonist, alleviated VH significantly in TC-IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC-IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC-IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.-Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.
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PMID:The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity. 3157 3